Spinal 5-HT3AR contributes to BmK I-induced inflammatory pain in rats.

Abstract

Subcutaneous injection of BmK I could be adopted to well establish a novel pain model. Moreover, 5-hydroxytryptamine (serotonin, 5-HT) receptor is involved in regulating animal pain-related behaviors. However, the underlying mechanism of 5-HT3R on BmK I-induced pain remains unclear. Animal behavioral testing, RT-PCR and Western blotting were used to yield the following results: first, intraplantar (i.pl.) injection of BmK I (10 μg) induced elevated mRNA and protein levels of 5-HT3AR in bilateral L4-L5 spinal cord; Second, intrathecal (i.t.) injection of ondansetron (a specific antagonist of 5-HT3AR) reduced spontaneous pain responses, attenuated unilateral thermal and bilateral mechanical hypersensitivity elicited by BmK I; Microglia could be activated by BmK I (i.pl.) in both sides of L4-L5 spinal cord, and this effect was reversed by intrathecal pre-treatment with 5-HT3AR antagonist. Meanwhile, the 5-HT3AR in L4-L5 spinal cord was almost co-localized with NeuN (a marker of nerve cell), but not co-expressed with Iba-1 (a marker of microglia). Finally, the expression level of CX3CL1 and CX3CR1 was reduced by intrathecal pre-treatment with ondansetron. Our results indicate that both 5-HT3AR signaling pathway and microglia are activated in the process of induction and maintenance of BmK I-induced pain nociception. Meanwhile, our results suggest that the neuronal 5-HT3AR may communicate with microglia indirectly via CX3CL1 which is involved in regulating the BmK I-induced hyperalgesia and sensitization.

• Authors: Jin Fu, Yun-Lu Jiao, Zheng-Wei Li, Yong-Hua Ji
• Journal: Sheng li xue bao : [Acta physiologica Sinica] (Sheng Li Xue Bao) Vol. 67 Issue 3 Pg. 283-94 (Jun 25 2015) ISSN: 0371-0874 [Print] China
• PMID: 26109301 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CX3CL1
• Cx3cl1 protein, rat
• Receptors, Serotonin, 5-HT3
• Scorpion Venoms
• makatoxin I

Topics

• Animals
• Behavior, Animal
• Chemokine CX3CL1 (metabolism)
• Hyperalgesia (chemically induced)
• Inflammation (physiopathology)
• Injections, Spinal
• Microglia (drug effects)
• Rats
• Rats, Sprague-Dawley
• Receptors, Serotonin, 5-HT3 (metabolism)
• Scorpion Venoms (adverse effects)
• Spinal Cord (metabolism, physiopathology)